| 1. |
- Bataille, Chris, et al.
(författare)
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A review of technology and policy deep decarbonization pathway options for making energy-intensive industry production consistent with the Paris Agreement
- 2018
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526. ; 187, s. 960-973
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Forskningsöversikt (refereegranskat)abstract
- The production of commodities by energy-intensive industry is responsible for 1/3 of annual global greenhouse gas (GHG) emissions. The climate goal of the Paris Agreement, to hold the increase in the global average temperature to well below 2 °C above pre-industrial levels while pursuing efforts to limit the temperature increase to 1.5 °C, requires global GHG emissions reach net-zero and probably negative by 2055–2080. Given the average economic lifetime of industrial facilities is 20 years or more, this indicates all new investment must be net-zero emitting by 2035–2060 or be compensated by negative emissions to guarantee GHG-neutrality. We argue, based on a sample portfolio of emerging and near-commercial technologies for each sector (largely based on zero carbon electricity & heat sources, biomass and carbon capture, and catalogued in an accompanying database), that reducing energy-intensive industrial GHG emissions to Paris Agreement compatible levels may not only be technically possible, but can be achieved with sufficient prioritization and policy effort. We then review policy options to drive innovation and investment in these technologies. From this we synthesize a preliminary integrated strategy for a managed transition with minimum stranded assets, unemployment, and social trauma that recognizes the competitive and globally traded nature of commodity production. The strategy includes: an initial policy commitment followed by a national and sectoral stakeholder driven pathway process to build commitment and identify opportunities based on local zero carbon resources; penetration of near-commercial technologies through increasing valuation of GHG material intensity through GHG pricing or tradable performance based regulations with protection for competitiveness and against carbon leakage; research and demand support for the output of pilot plants, including some combination of guaranteed above-market prices that decline with output and an increasing requirement for low carbon inputs in government procurement; and finally, key supporting institutions.
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| 2. |
- Bennett, Charles L., et al.
(författare)
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Reassessments of ESAs for cancer treatment in the US and Europe
- 2010
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Ingår i: Oncology. - 0890-9091. ; 24:3, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- Anemia is a widely prevalent complication among cancer patients. At the time of diagnosis, 30% to 40% of patients with non-Hodgkin lymphoma or Hodgkin lymphoma and up to 70% of patients with multiple myeloma are anemic; rates are higher among persons with myelodysplastic syndromes. Among patients with solid cancers or lymphomas, up to half develop anemia following chemotherapy. For almost 2 decades, erythropoiesis-stimulating agents (ESAs) were the primary treatment for cancer-related anemia. However, reassessments of benefits and risks of ESAs for cancer-associated anemia have occurred internationally. We reviewed guidelines and notifications from regulatory agencies and manufacturers, reimbursement policies, and utilization for ESAs in the cancer and chronic kidney disease settings within the United States, Europe, and Canada. In 2008 the US Food and Drug Administration (FDA) restricted ESAs from cancer patients seeking cure. Reimbursement is limited to hemoglobin levels < 10 g/dL. In the United States, ESA usage increased 340% between 2001 and 2006, and decreased 60% since 2007. The European Medicines Agency (EMEA) recommended that ESA benefits do not outweigh risks. In Europe between 2001 and 2006, ESA use increased 51%; since 2006, use decreased by 10%. In 2009, Canadian manufacturers recommended usage based on patient preferences. In Canada in 2007, approximately 20% of anemic cancer patients received ESAs, a 20% increase since 2004. In contrast to Europe, where ESA use has increased over time, reassessments of ESA-associated safety concerns in the United States have resulted in marked decrements in ESA use among cancer patients.
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| 3. |
- De Bono, Johann S., et al.
(författare)
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Cabazitaxel shows a consistently greater survival benefit compared to mitoxantrone in patients with mCRPC
- 2014
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Ingår i: Nowotwory. - : Via Medica. - 0029-540X. ; 64:1, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Aim: This sub analysis of TROPIC study evaluates overall survival (OS) under cabazitaxel in patients who had no initial response to docetaxel (D ) and discontinued D for disease progression and those who initially responded to D but experienced disease progression <3 months since last D dose. These patients are believed unlikely to benefit from D re-treatment and need new treatment options such as cabazitaxel.Methods: Of the 755 patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled in TROPIC study, 362 (47.9%) had no initial response to D and discontinued it for disease progression, 155 (20.5%) had an initial response to D therapy according to investigator judgment but progressed <3 months since last D dose and 238 (31.5%) did not belong to these two subgroups. All patients were randomized to receive cabazitaxel 25 mg/m2 or mitoxantrone 12 mg/m2 both every 3 weeks and prednisone 10 mg per os daily.Results: Median OS with cabazitaxel was consistently longer than with mitoxantrone in all subgroups. The highest survival benefit versus mitoxantrone was observed for patients who initially responded to D and then progressed <3 months since last D dose (median OS 15.7 versus 11.6 months, Hazard ratio (HR) 0.52 [95% CI 0.35-0.76]). Median PFS was also significantly improved in the latter subgroup compared to mitoxantrone (2.6 versus 1.4 months, HR 0.66 [0.48-0.91]).Conclusion: Cabazitaxel plus prednisone consistently shows a greater survival benefit compared to mitoxantrone plus prednisone whatever the subgroup considered, including responders to first-line D who progressed <3 months since last D and pts without initial response to D who discontinued it for disease progression.
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| 4. |
- Fanti, Stefano, et al.
(författare)
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EAU-EANM Consensus Statements on the Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Patients with Prostate Cancer and with Respect to [177Lu]Lu-PSMA Radioligand Therapy
- 2022
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Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:5, s. 530-536
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is useful for selected clinical indications in patients with prostate cancer (PCa) but it may have broader clinical utility owing to the emergence of lutetium-177-PSMA-617 ([177Lu]Lu-PSMA) therapy. However, robust data regarding the impact of PSMA PET/CT on patient management and treatment are lacking, and in many areas, the role of next-generation imaging has not been defined. OBJECTIVE: To assess expert opinion on the use of PSMA-based imaging and therapy to develop interim guidance. DESIGN, SETTING, AND PARTICIPANTS: A panel of 21 PCa experts from various disciplines received thematic topics and relevant literature. A questionnaire to assess proposed guidance statements regarding PSMA PET/CT and [177Lu]Lu-PSMA therapy was developed for completion remotely in a first e-Delphi round. A subsequent panel discussion was conducted during a 1-d meeting, which included a second Delphi round. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Panellists voted anonymously on statements using a nine-point Likert scale from 1 = strongly disagree to 9 = strongly agree. Median scores were calculated and consensus was assessed using methods proposed by the Research and Development (RAND) corporation. RESULTS AND LIMITATIONS: Statements were developed to cover the following topics: PSMA PET/CT utility, clinical use, and choice of tracer; patient selection; and management of patients receiving [177Lu]Lu-PSMA for metastatic PCa. Consensus was reached for 33/36 statements. In-group bias is a potential limitation, as some statements were rephrased during discussions at the 1-d meeting. CONCLUSIONS: Adoption of PSMA PET/CT as an imaging tool to guide [177Lu]Lu-PSMA therapy should be supported by indications for appropriate use. PATIENT SUMMARY: A panel of experts in prostate cancer reached a consensus for the majority of statements proposed regarding the role of prostate-specific membrane antigen (PSMA)-based imaging and therapy, particularly the use of PSMA-based imaging in patients suitable for [177Lu]Lu-PSMA therapy and the need to perform PSMA-based imaging before considering patients as candidates for this therapy.
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| 5. |
- Neuhoff, Karsten, et al.
(författare)
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Inclusion of Consumption of carbon intensive materials in emissions trading – An option for carbon pricing post-2020
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- A project led jointly by Climate Strategies and DIW Berlin has been exploring whether inclusion of domestic sales of selected energy intensive commodities (e.g. steel) in domestic emission trading schemes is an effective and feasible approach towards restoring the carbon price signal in these sectors, without damaging competitiveness. It has been delivered by a multidisciplinary, international team of researchers from a number of institutions, representing various fields (EU law and institutions, climate policy and economics, energy market and infrastructure policy and economics).
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| 6. |
- Oprea-Lager, Daniela Elena, et al.
(författare)
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European Association of Nuclear Medicine Focus 5 : Consensus on Molecular Imaging and Theranostics in Prostate Cancer
- 2024
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Ingår i: European Urology. - 0302-2838. ; 85:1, s. 49-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: In prostate cancer (PCa), questions remain on indications for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging and PSMA radioligand therapy, integration of advanced imaging in nomogram-based decision-making, dosimetry, and development of new theranostic applications. Objective: We aimed to critically review developments in molecular hybrid imaging and systemic radioligand therapy, to reach a multidisciplinary consensus on the current state of the art in PCa. Design, setting, and participants: The results of a systematic literature search informed a two-round Delphi process with a panel of 28 PCa experts in medical or radiation oncology, urology, radiology, medical physics, and nuclear medicine. The results were discussed and ratified in a consensus meeting. Outcome measurements and statistical analysis: Forty-eight statements were scored on a Likert agreement scale and six as ranking options. Agreement statements were analysed using the RAND appropriateness method. Ranking statements were analysed using weighted summed scores. Results and limitations: After two Delphi rounds, there was consensus on 42/48 (87.5%) of the statements. The expert panel recommends PSMA PET to be used for staging the majority of patients with unfavourable intermediate and high risk, and for restaging of suspected recurrent PCa. There was consensus that oligometastatic disease should be defined as up to five metastases, even using advanced imaging modalities. The group agreed that [177Lu]Lu-PSMA should not be administered only after progression to cabazitaxel and that [223Ra]RaCl2 remains a valid therapeutic option in bone-only metastatic castration-resistant PCa. Uncertainty remains on various topics, including the need for concordant findings on both [18F]FDG and PSMA PET prior to [177Lu]Lu-PSMA therapy. Conclusions: There was a high proportion of agreement among a panel of experts on the use of molecular imaging and theranostics in PCa. Although consensus statements cannot replace high-certainty evidence, these can aid in the interpretation and dissemination of best practice from centres of excellence to the wider clinical community. Patient summary: There are situations when dealing with prostate cancer (PCa) where both the doctors who diagnose and track the disease development and response to treatment, and those who give treatments are unsure about what the best course of action is. Examples include what methods they should use to obtain images of the cancer and what to do when the cancer has returned or spread. We reviewed published research studies and provided a summary to a panel of experts in imaging and treating PCa. We also used the research summary to develop a questionnaire whereby we asked the experts to state whether or not they agreed with a list of statements. We used these results to provide guidance to other health care professionals on how best to image men with PCa and what treatments to give, when, and in what order, based on the information the images provide.
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| 7. |
- Parker, Christopher C., et al.
(författare)
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Three-year Safety of Radium-223 Dichloride in Patients with Castration-resistant Prostate Cancer and Symptomatic Bone Metastases from Phase 3 Randomized Alpharadin in Symptomatic Prostate Cancer Trial
- 2018
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 73:3, s. 427-435
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Tidskriftsartikel (refereegranskat)abstract
- Background: In Alpharadin in Symptomatic Prostate Cancer (ALSYMPCA) trial, radium-223 versus placebo prolonged overall survival with favorable safety in castration-resistant prostate cancer patients with symptomatic bone metastases. Long-term radium-223 monitoring underlies a comprehensive safety and risk/benefit assessment. Objective: To report updated ALSYMPCA safety, including long-term safety up to 3 yr after the first injection. Design, setting, and participants: Safety analyses from phase 3 randomized ALSYMPCA trial included patients receiving >= 1 study-drug injection (600 radium-223 and 301 placebo). Patients (405 radium-223 and 167 placebo) entered long-term safety follow-up starting 12 wk after the last study-drug injection, to 3 yr from the first injection. Forty-eight of 405 (12%) radium-223 and 12/167 (7%) placebo patients completed follow-up, with evaluations every 2 mo for 6 mo, then every 4 mo until 3 yr. Outcome measurements and statistical analysis: All adverse events (AEs) were collected until 12 wk after the last injection; subsequently, only treatment-related AEs were collected. Additional long-term safety was assessed by development of acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), aplastic anemia, and secondary malignancies. Data analysis used descriptive statistics. Results and limitations: During treatment to 12 wk following the last injection, 564/600 (94%) radium-223 and 292/301 (97%) placebo patients had treatment-emergent AEs (TEAEs). Myelosuppression incidence was low. Grade 3/4 hematologic TEAEs in radium-223 and placebo groups were anemia (13% vs 13%), neutropenia (2% vs 1%), and thrombocytopenia (7% vs 2%). Ninety-eight of 600 (16%) radium-223 and 68/301 (23%) placebo patients experienced grade 5 TEAEs. Long-term follow-up showed no AML, MDS, or new primary bone cancer; secondary non-treatment-related malignancies occurred in four radium-223 and three placebo patients. One radium-223 patient had aplastic anemia 16 mo after the last injection. No other cases were observed. Limitations include short (3-yr) follow-up. Conclusions: Final long-term safety ALSYMPCA analysis shows that radium-223 remained well tolerated, with low myelosuppression incidence and no new safety concerns.
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| 8. |
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| 9. |
- Sartor, Oliver, et al.
(författare)
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Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases : results from a phase 3, double-blind, randomised trial
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:7, s. 738-746
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Tidskriftsartikel (refereegranskat)abstract
- Background Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range a-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases. Methods In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2: 1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751. Findings Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15.6 months [95% CI 13.5-18.0] vs 9.8 months [7.3-23.7]; hazard ratio [HR] = 0.66, 95% CI 0.52-0.83; p = 0.00037). The risks of external beam radiation therapy for bone pain (HR 0.67, 95% CI 0.53-0.85) and spinal cord compression (HR = 0.52, 95% CI 0.29-0.93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0.62, 95% CI 0.35-1.09), or the need for tumour-related orthopaedic surgical intervention (HR 0.72, 95% CI 0.28-1.82). Interpretation Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.
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| 10. |
- Sartor, Oliver, et al.
(författare)
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Re-treatment with radium-223 : 2-year follow-up from an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases
- 2019
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Ingår i: The Prostate. - : Wiley Periodicals. - 0270-4137 .- 1097-0045. ; 79:14, s. 1683-1691
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Tidskriftsartikel (refereegranskat)abstract
- Background: Radium-223 dichloride (radium-223) is approved for patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no visceral disease using a dosing regimen of 6 injections (55 kBq/kg intravenously; 1 injection every 4 weeks). Early results from international, open-label, phase 1/2 study NCT01934790 showed that re-treatment with radium-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from 2-year follow-up of the radium-223 re-treatment study.Methods: Patients with CRPC and bone metastases who completed 6 initial radium-223 injections with no disease progression in bone and later progressed were eligible for radium-223 re-treatment (up to 6 additional radium-223 injections), provided that hematologic parameters were adequate and chemotherapy had not been administered after the initial course of radium-223. Concomitant cytotoxic agents were not allowed during re-treatment but were allowed at the investigator's discretion during follow-up; other concomitant agents for prostate cancer (including abiraterone acetate or enzalutamide) were allowed at investigator's discretion. The primary objective was safety. Exploratory objectives included time to radiographic bone progression, radiographic progression-free survival (rPFS), time to total alkaline phosphatase (tALP), and prostate-specific antigen (PSA) progression, overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-treatment start. Evaluation of safety and exploratory efficacy objectives included active 2-year follow-up. Safety results from active follow-up and updated efficacy are reported.Results: Overall, 44 patients were re-treated with radium-223; 29 (66%) completed all 6 injections, and 34 (77%) entered 2-year active follow-up, during which no new safety concerns and no serious drug-related adverse events were noted. rPFS events (progression or death) occurred in 19 (43%) of 44 patients; median rPFS was 9.9 months. Radiographic bone progression occurred in 5 (11%) of 44 patients. Median OS was 24.4 months. Median times to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Median time to tALP progression was not reached; median time to PSA progression was 2.2 months.Conclusions: Re-treatment with radium-223 in this selected patient population was well tolerated, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up.
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